Kinugasa reactions

Copper (II) salts proved to be efficient catalysts in the Kinugasa reaction, and this allowed the reaction to be performed under practical and convenient conditions. Amines strongly influence diastereoselectivity, enantioselectivity, and reaction rate. Bulkier amines always give better diastereoselection and, generally, tertiary amines provide higher diastereoselectivity than secondary ones, and the... 

Scheme 69 Preparation of tricyclic P-lactams 193 using Kinugasa reaction...

A synthetic route to p-lactam-fused enediynes by intramolecular Kinugasa reaction has been successfully developed. The method has widened the scope of the Kinugasa reaction in the synthesis of sensitive systems like tricycle 193 (Scheme 69) [100]. 

Kinugasa reaction. The Kinugasa reaction consists in the coupling of nitrones with propargyl moieties catalyzed by copper salts (Scheme 5). 

In 2005, the Kinugasa reaction performed on /V-propargyl nucleobases, such as adenine, uracil, and thymine derivatives, with diphenyl nitrone has been reported to produce cis- and trans-(3-lactam nucleosides (Scheme 63), [157]. 

The ynamide-Kinugasa reaction has been used for the highly stereoselective synthesis of chiral cz-amino- (3-1 actams. The application of this reaction consists in the preparation of chiral a-amino-2-azetidinones starting from chiral ynamide (Scheme 64), [158]. 

Scheme 63 Synthesis of (3-lactam nucleosides via Kinugasa reaction...

Scheme 64 Synthesis of a-amino-(3-lactams via ynamide-Kinugasa reaction...

The Kinugasa reaction has emerged as a useful route to /3-lactams and its use has been reviewed <2004AGE2198>. The reaction has been used as a method by which the 4/6/6 system 450 was obtained from 451 with high ee <2004AGE2198>. 

The Kinugasa reaction has been used as well for the asymmetric synthesis of P-lactams 25 via cycloaddition between chiral oxazolidinyl propynes and nitrones, in the presence of copper chloride <02TL5499>. 

On account of their very important biological activity, /9-lactams are important synthetic targets [4-9]. Fused polycyclic -lactam subunits appear in many natural products such as penicillins [4-6] and trinems/tribac-tams [10-13]. Fu et al. reported that such frameworks can be prepared with high levels of enantioselectivity via the intramolecular Kinugasa reaction [ 14, 15] of alkyne-nitrone in the presence of a planar chiral Cu/phosphaferrocene-oxazoline catalyst [16]. For instance, compound 1 was transformed into tricyclic /9-lactam 3 in good stereoselectivity and yielded (88% ee and 74% yield) using 5 mol % of CuBr and 5.5 mol % of complex 2 (Scheme 1). 

Coyne AG, Miiller-Bunz H, Guiry PJ (2007) The asymmetric synthesis of p-lactams HETPHOX/Cu(I) mediated synthesis via the Kinugasa reaction. Tetrahedron-As5mmietr 18 199-207... 

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